Scutellaria baicalensis (Huang Qin or Scullcap) is a widely used Chinese herb which has been shown to have anti-cancer and anti-inflammatory activities. However, its mechanism, efficacy, and safety have not been scientifically evaluated. Our recent studies reveal that Scutellaria baicalensis and its flavonoid components strongly inhibit the synthesis of prostaglandin E2 (PGEZ) via the cyclooxygenase-2 (COX-2) pathway. We have demonstrated that Scutellaria baicalensis inhibited the growth of HNSCC cells in vitro and in vivo (xenografts in nude mice). Therefore, we developed a testable hypothesis that Scutellaria baicalensis inhibits PGE2 via modulation of COX-2 pathway, thereby, inhibiting HNSCC cell growth by blocking cell proliferation (GI arrest) and promoting programmed cell death (apoptosis). The rationale for the proposed studies is based on the fact that HNSCC overproduces PGE2 and that the specific inhibitors against COX-2 suppress cancer cell growth. The objectives of this study are to elucidate the molecular mechanism of anti-cancer effects of Scutellaria baicalensis and to evaluate its efficacy and safety in animals. The first aim (in vitro studies) is to determine whether the inhibitory activity of Scutellaria baicalensis on COX-2 pathway is through direct inhibition of COX-2 or through the downregulation of COX-2 expression. The second aim (animal studies) is to determine anti-cancer efficacy of Scutellaria baicalensis in nude mice with HNSCC xenografts by examining tumor volume, cell proliferation (PCNA), apoptosis (TUNEL), and PGE2 level (EIA/in situ RAM). The third aim (animal studies) is to determine its pharmacokinetics and toxicity (short term and long term). The completion of this study will allow us to better understand the molecular mechanisms of the anticancer activities of Scutellaria baicalensis and to determine the maximal effective dose and maximal tolerated dose that will be used to guide future clinical trials.